Paraoxonase 1 gene polymorphisms concerning non-insulin-dependent diabetes mellitus nephropathy in hemodialysis patients. 2020

Alicja E Grzegorzewska, and Kamila Ostromecka, and Paulina Adamska, and Adrianna Mostowska, and Wojciech Warchoł, and Paweł P Jagodziński
Department of Nephrology, Transplantology and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznań, Przybyszewskiego 49, Poland. Electronic address: agrzegorzewska@ump.edu.pl.

Data on involvement of paraoxonase 1 gene (PON1) in non-insulin-dependent diabetes mellitus (NIDDM) nephropathy are scarce. We investigated PON1 polymorphisms concerning end-stage NIDDM nephropathy and atherosclerotic complications in NIDDM nephropathy patients treated with hemodialysis (HD). In NIDDM nephropathy (n = 402) and non-diabetic (n = 998) HD subjects, we obtained PON1 polymorphisms by HRM analysis (rs662) or predesigned TaqMan SNV Genotyping Assay (rs854560, rs705379). Only PON1 rs705379 was associated with end-stage NIDDM nephropathy in the recessive (OR 1.451, 95% CI 1.104-1.906, P = 0.009) and additive (OR 1.398, 95%CI 1.009-1.936, P = 0.046) inheritance modes. NIDDM nephropathy patients bearing the rs854560 T allele were at higher risk for ischemic cerebral stroke (OR 2.087, 95%CI 1.145-3.801, P = 0.016). In non-diabetic patients but not NIDDM nephropathy subjects, atherogenic dyslipidemia corresponded with PON1 rs662 A allele and PON1 rs854560 TT homozygosity. In HD patients, NIDDM nephropathy correlates with the TT genotype of PON1 rs705379. The rs854560 T allele indicates a higher risk for atherosclerotic diseases in NIDDM nephropathy subjects. The T alleles of both PON1 SNVs are known as low expression variants downregulated serum PON1 activity. An increase of diminished PON1 activity may be a target in the prevention of NIDDM nephropathy and NIDDM atherosclerotic complications.

UI MeSH Term Description Entries
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D003924 Diabetes Mellitus, Type 2 A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY. Diabetes Mellitus, Adult-Onset,Diabetes Mellitus, Ketosis-Resistant,Diabetes Mellitus, Maturity-Onset,Diabetes Mellitus, Non-Insulin-Dependent,Diabetes Mellitus, Slow-Onset,Diabetes Mellitus, Stable,MODY,Maturity-Onset Diabetes Mellitus,NIDDM,Diabetes Mellitus, Non Insulin Dependent,Diabetes Mellitus, Noninsulin Dependent,Diabetes Mellitus, Noninsulin-Dependent,Diabetes Mellitus, Type II,Maturity-Onset Diabetes,Noninsulin-Dependent Diabetes Mellitus,Type 2 Diabetes,Type 2 Diabetes Mellitus,Adult-Onset Diabetes Mellitus,Diabetes Mellitus, Adult Onset,Diabetes Mellitus, Ketosis Resistant,Diabetes Mellitus, Maturity Onset,Diabetes Mellitus, Slow Onset,Diabetes, Maturity-Onset,Diabetes, Type 2,Ketosis-Resistant Diabetes Mellitus,Maturity Onset Diabetes,Maturity Onset Diabetes Mellitus,Non-Insulin-Dependent Diabetes Mellitus,Noninsulin Dependent Diabetes Mellitus,Slow-Onset Diabetes Mellitus,Stable Diabetes Mellitus
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D006435 Renal Dialysis Therapy for the insufficient cleansing of the BLOOD by the kidneys based on dialysis and including hemodialysis, PERITONEAL DIALYSIS, and HEMODIAFILTRATION. Dialysis, Extracorporeal,Dialysis, Renal,Extracorporeal Dialysis,Hemodialysis,Dialyses, Extracorporeal,Dialyses, Renal,Extracorporeal Dialyses,Hemodialyses,Renal Dialyses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D043303 Aryldialkylphosphatase An enzyme which catalyzes the hydrolysis of an aryl-dialkyl phosphate to form dialkyl phosphate and an aryl alcohol. It can hydrolyze a broad spectrum of organophosphate substrates and a number of aromatic carboxylic acid esters. It may also mediate an enzymatic protection of LOW DENSITY LIPOPROTEINS against oxidative modification and the consequent series of events leading to ATHEROMA formation. The enzyme was previously regarded to be identical with Arylesterase (EC 3.1.1.2). Aryl-dialkyl Phosphatase,Arylalkylphosphatase,Homocysteine Thiolactone Hydrolase,OPA Anhydrase,OPH Enzyme,Organophosphorus Acid Anhydrase,Organophosphorus Acid Anhydrolase,Organophosphorus Acid Hydrolase,Organophosphorus Hydrolase,Paraoxonase,Paraoxonase-1,Paraoxonase-2,Acid Anhydrase, Organophosphorus,Acid Anhydrolase, Organophosphorus,Acid Hydrolase, Organophosphorus,Anhydrase, OPA,Anhydrase, Organophosphorus Acid,Anhydrolase, Organophosphorus Acid,Aryl dialkyl Phosphatase,Enzyme, OPH,Hydrolase, Homocysteine Thiolactone,Hydrolase, Organophosphorus,Hydrolase, Organophosphorus Acid,Paraoxonase 1,Paraoxonase 2,Phosphatase, Aryl-dialkyl,Thiolactone Hydrolase, Homocysteine
D050197 Atherosclerosis A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA. Atherogenesis,Atherogeneses,Atheroscleroses

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